The present invention relates to substituted C-imidazo[1,2-a]pyridin-3-yl-methylamines and their physiologically acceptable salts, processes for their preparation, medicaments comprising these compounds and the use of substituted C-imidazo[1,2-a]pyridin-3-yl-methylamines for the preparation of medicaments.
Nitrogen monoxide (NO) regulates numerous physiological processes, inter alia neurotransmission, relaxation and proliferation of the smooth musculature, adhesion and aggregation of thrombocytes as well as tissue injury and inflammation. On the basis of the large number of signal functions, nitrogen monoxide is associated with a number of diseases, for example in L. J. Ignarro, Angew. Chem. (1999), 111, pages 2002-2013 and in F. Murad, Angew. Chem. Int. Ed. (1999), 111, pages 1976-1989. The enzyme which is responsible for the physiological formation of nitrogen monoxide, nitrogen monoxide synthase (NO synthase), plays an important role in this context in the therapeutic influencing of these diseases. Three different iso forms of NO synthase have so far been identified, namely the two constitutive forms nNO synthase and eNO synthase and the inducible form iNO synthase (A. J. Hobbs, A. Higgs, S. Moncada, Annu. Rev. Pharmacol. Toxicol. (1999), 39, pages 191-220; I. C. Green, P.-E. Chabrier, DDT (1999), 4, pages 47-49; P.-E. Chabrier et al., Cell. Mol. Life Sci. (1999), 55, pages 1029-1035).
The inhibition of NO synthase opens up new therapy schemes for various diseases associated with nitrogen monoxide (A. J. Hobbs et al., Annu. Rev. Pharmacol. Toxicol. (1999), 39, pages 191-220; I. C. Green, P.-E. Chabrier, DDT (1999), 4, pages 47-49; P.-E. Chabrier et al., Cell. Mol. Life Sci. (1999), 55, pages 1029-1035), such as, for example, migraine (L. L. Thomsen, J. Olesen, Clinical Neuroscience (1998), 5, pages 28-33; L. H. Lassen et al., The Lancet (1997), 349, 401-402), septic shock, neurodegenerative diseases, such as multiple sclerosis, Parkinson's disease, Alzheimer's disease or Huntington's disease, inflammations, inflammatory pain, cerebral ischaemia, diabetes, meningitis and arteriosclerosis. Furthermore, inhibition of NO synthase can have an effect on wound healing, on tumours and on angiogenesis, and can cause a non-specific immunity to microorganisms (A. J. Hobbs et al., Annu. Rev. Pharmacol. Toxicol. (1999), 39, pages 191-220).
Active compounds known to date which inhibit NO synthase include, in addition to L-NMMA and L-NAME—i.e. analogues of L-arginine from which nitrogen monoxide and citrulline are formed in vivo with the involvement of NO synthase—inter alia S-methyl-L-citrulline, aminoguanidine, S-methylisourea, 7-nitroindazole and 2-mercaptoethylguanidine (A. J. Hobbs et al., Annu. Rev. Pharmacol. Toxicol. (1999), 39, pages 191-220).